Division of Infectious Diseases, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, 108-8639, Tokyo, Japan.
Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, 5-1-5 Kashiwanoha Kashiwa 277, 8562, Chiba, Japan.
Virol J. 2023 Jul 13;20(1):146. doi: 10.1186/s12985-023-02113-z.
The mucosa serves as the first defence against pathogens and facilitates the surveillance and elimination of symbiotic bacteria by mucosal immunity. Recently, the mRNA vaccine against SARS-CoV-2 has been demonstrated to induce secretory antibodies in the oral and nasal cavities in addition to a systemic immune response. However, the mechanism of induced immune stimulation effect on mucosal immunity and commensal bacteria profile remains unclear.
Here, we longitudinally analysed the changing nasal microbiota and both systemic and nasal immune response upon SARS-CoV-2 mRNA vaccination, and evaluated how mRNA vaccination influenced nasal microbiota in 18 healthy participants who had received the third BNT162b.
The nasal S-RBD IgG level correlated significantly with plasma IgG levels until 1 month and the levels were sustained for 3 months post-vaccination. In contrast, nasal S-RBD IgA induction peaked at 1 month, albeit slightly, and correlated only with plasma IgA, but the induction level decreased markedly at 3 months post-vaccination. 16 S rRNA sequencing of the nasal microbiota post-vaccination revealed not an overall change, but a decrease in certain opportunistic bacteria, mainly Fusobacterium. The decrease in these bacteria was more pronounced in those who exhibited nasal S-RBD IgA induction, and those with higher S-RBD IgA induction had lower relative amounts of potentially pathogenic bacteria such as Pseudomonas pre-vaccination. In addition, plasma and mucosal S-RBD IgG levels correlated with decreased commensal pathogens such as Finegoldia.
These findings suggest that the third dose of SARS-CoV-2 mRNA vaccination induced S-RBD antibodies in the nasal mucosa and may have stimulated mucosal immunity against opportunistic bacterial pathogens. This effect, albeit probably secondary, may be considered one of the benefits of mRNA vaccination. Furthermore, our data suggest that a cooperative function of mucosal and systemic immunity in the reduction of bacteria and provides a better understanding of the symbiotic relationship between the host and bacteria in the nasal mucosa.
黏膜作为第一道防线抵御病原体,并通过黏膜免疫来监视和清除共生菌。最近,SARS-CoV-2 的 mRNA 疫苗已被证明除了诱导全身免疫反应外,还能在鼻腔和口腔中诱导分泌型抗体。然而,诱导免疫刺激对黏膜免疫和共生菌谱的机制仍不清楚。
在这里,我们纵向分析了 18 名接受第三次 BNT162b 接种的健康参与者的 SARS-CoV-2 mRNA 接种后鼻腔微生物群和全身及鼻腔免疫反应的变化,并评估了 mRNA 接种如何影响鼻腔微生物群。
鼻腔 S-RBD IgG 水平与血浆 IgG 水平显著相关,直至 1 个月,并且在接种疫苗后 3 个月内持续。相比之下,鼻腔 S-RBD IgA 的诱导在 1 个月时达到峰值,尽管略有升高,并且仅与血浆 IgA 相关,但在接种疫苗后 3 个月时显著下降。接种疫苗后鼻腔微生物群的 16S rRNA 测序显示,不是整体变化,而是某些机会性病原体(主要是梭杆菌)的减少。在表现出鼻腔 S-RBD IgA 诱导的个体中,这些细菌的减少更为明显,并且在接种疫苗前,具有较高 S-RBD IgA 诱导的个体中,潜在致病性细菌(如假单胞菌)的相对丰度较低。此外,血浆和黏膜 S-RBD IgG 水平与丰度降低的共生病原体(如法氏囊菌)相关。
这些发现表明,第三剂 SARS-CoV-2 mRNA 疫苗在鼻腔黏膜中诱导了 S-RBD 抗体,并可能刺激了针对机会性病原体的黏膜免疫。这种效应,尽管可能是次要的,但可能被认为是 mRNA 疫苗的益处之一。此外,我们的数据表明,黏膜和全身免疫在减少细菌方面具有协同作用,并提供了对宿主和鼻腔黏膜中细菌共生关系的更好理解。